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Objective: To summarize the clinical characteristics, treatment response and prognostic factors of rhabdomyosarcoma (RMS) in children. Methods: The clinical characteristics such as age at diagnosis, primary tumor site, tumor size, pathological type, clinical stage, and risk grouping of 213 RMS patients (140 males and 73 females) treated in Hematology Oncology Center of Beijing Children's Hospital, Capital Medical University, from May 2006 to June 2018 were analyzed retrospectively. The clinical characteristics, overall survival (OS), event free survival (EFS) and prognostic factors of children treated with the Beijing Children's Hospital-Rhabdomyosarcoma (BCH-RMS) regimen were analyzed. Survival data were analyzed by Kaplan-Meier survival analysis, and single factor analysis was performed by Log-Rank test. Results: The diagnostic age of 213 cases was 48.0 months (ranged 3.0-187.5 months), of which 136 cases (63.8%) were younger than 10 years old. The head and neck region was the most common primary site of tumor (30%, 64 cases), followed by the genitourinary tract (26.8%, 57 cases). Among pathological subtypes, embryonal RMS accounted for 71.4% (152 cases), while alveolar RMS and anaplastic RMS accounted for only 26.8% (57 cases) and 1.9% (4 cases), respectively. According to the Intergroup Rhabdomyosarcoma Study Group (IRS), IRS-Ⅲ and Ⅳ accounted for 85.0% (181 cases) of all RMS patients. In all patients, 9.4% (20 cases) patients were divided in to low-risk group, 52.1% (111 cases) patients in to intermediate -risk group, 25.8% (55 cases) patients in to high-risk group, and 12.7% (27 cases) patients in to the central nervous system invasion group, respectively. All patients with RMS received chemotherapy. The cycles of chemotherapy were 13.5 (ranged 5.0-18.0) for patients without event occurrence, while 14.2 (ranged 3.0-30.0) for patients with event occurrence. Among the 213 patients, 200 patients had surgical operation, of whom 103 patients underwent surgery before chemotherapy and 97 patients at the end of chemotherapy, 21 patients had secondary surgical resection. Radiotherapy was performed in 114 patients. The follow-up time was 23.0 months (ranged 0.5-151.0 months) . There were 98 patients with relapsed or progressed disease and 67 patients with death. The median time to progression was 10 months, of which 67 (68.4%) relapse occurred within 1 year and no recurrence occurred after follow-up for more than 5 years. The 3-year EFS and 5-year EFS were (52±4) % and (48±4) %, while the 3-year OS and 5-year OS were (65±4) % and (64±4) % by survival analysis. The 5-year OS of the low-risk, intermediate-risk, the high-risk were 100%, (74±5) %, (48±8) %, and the 2-year OS of the central nervous system invasion group was (36±11) % (χ(2)=33.52, P< 0.01). The 5-year EFS of the low-risk, intermediate-risk, the high-risk were (93±6) %, (51±5) %, (36±7) % and the 2-year EFS of the central nervous system invasion group was (31±10) % (χ(2)=24.73, P< 0.01) . Survival factor analysis suggested that the OS of children was correlated with age(χ(2)=4.16, P =0.038), tumor TNM stage (χ(2)=22.02, P= 0.001), IRS group (χ(2)=4.49, P< 0.01) and the risk group (χ(2)=33.52, P< 0.01). Conclusions: This study showed that the median age of newly diagnosed RMS patients was 4 years. The head and neck and the genitourinary tract were the most common primary origin of RMS. The OS was low in single-center RMS children. The median time to recurrence was 10 months, and recurrence was rare 3 years later.

Background: Pediatric paired box 3:forkhead box protein O1 fusion-negative (PF-) rhabdomyosarcoma (RMS) represents a diverse spectrum of tumors with marked differences in histology, myogenic differentiation, and clinical behavior., Methods: This study sought to evaluate the clinical and mutational spectrum of 24 pediatric PF- human RMS tumors with high levels of myogenic differentiation. Tumors were sequenced with OncoPanel v.2, a panel consisting of the coding regions of 504 genes previously linked to human cancer., Results: Most of the tumors (19 of 24) arose at head/neck or genitourinary sites, and the overall survival rate was 100% with a median follow-up time of 4.6 years (range, 1.4-8.6 years). RAS pathway gene mutations were the most common mutations in PF-, highly differentiated RMS tumors. In addition, Hedgehog (Hh) and mechanistic target of rapamycin (mTOR) gene mutations with evidence for functional relevance (high-impact) were identified in subsets of tumors. The presence of Hh and mTOR pathway gene mutations was mutually exclusive and was associated with high-impact RAS pathway gene mutations in 3 of 4 Hh-mutated tumors and in 1 of 6 mTOR-mutated tumors., Conclusions: Interestingly, Hh and mTOR gene mutations were previously associated with rhabdomyomas, which are also known to preferentially arise at head/neck and genitourinary sites. Findings from this study further support the idea that PF-, highly differentiated RMS tumors and rhabdomyomas may represent a continuous spectrum of tumors. Cancer 2018;124:1973-81. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Objective: Pediatric genitourinary rhabdomyosarcoma (RMS) accounts for 25 % of all pediatric soft tissue sarcomas. The treatment of these tumors has shifted over time from debilitating radical exenteration to organ-sparing techniques using multimodal therapy. Our review aims to summarize recent relevant literature regarding the current treatment practices of pediatric genitourinary RMS and how these practices have shifted over time., Methods: PubMed database search was utilized to identify relevant literature from 1997 to 2015 relating to the treatment of pediatric genitourinary RMS with emphasis on organ preservation and maintaining organ function., Results: A total of 31 articles from 1997 through 2015 were identified relating to current management concepts in pediatric genitourinary sarcomas. Relevant articles were reviewed in detail and discussed., Conclusion: The treatment of pediatric genitourinary RMS has shifted from debilitating pelvic exenteration to a multimodal treatment approach involving surgery, chemotherapy, and radiation therapy in an effort to preserve genitourinary organs and reduce treatment morbidity. Continued research is required to improve post-treatment organ function. Further studies utilizing objective urodynamic evaluation are necessary to better characterize bladder function after treatment for RMS. Exciting recent developments in RMS research of fusion proteins that induce cell transformation and inhibit apoptosis and myogenic differentiation may result in future management changes to treatment protocols.

Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in infants and children and the third most common pediatric solid tumor, accounting for 5% to 15% of all childhood solid tumors. Of these, 15% to 20% arise from the genitourinary tract, with the most common sites originating from the prostate, bladder, and paratesticular regions, followed by the vagina and uterus. Although upfront radical surgery was used at the initiation of Intergroup RMS Study-I (1972-1978), the treatment paradigm has shifted to include initial biopsy with the goal of organ preservation, systemic chemotherapy for all patients, and local control involving surgical resection with or without radiation therapy for most patients. Collaborative group clinical trials have led to dramatic improvement in survival rates from 1960 to 1996 among patients with low- or intermediate-risk disease; however, outcomes appear to have plateaued in more recent years, and the prognosis for patients with metastatic or relapsed/refractory disease remains poor. Current management goals include minimizing toxicity while maintaining the excellent outcomes in low-risk disease, as well as improving outcomes in patients with intermediate- and high-risk disease. Advances in genetic analysis have allowed further refinement in risk stratification of patients. Perhaps the most significant recent development in RMS research was the discovery of an association of alveolar RMS (ARMS) with translocations t(2;13) and t(1;13). Translocation fusion-positive tumors comprise 80% of ARMS and are more aggressive. Fusion-negative ARMS may have a clinical course similar to embryonal RMS. Future Children's Oncology Group sarcoma studies will likely incorporate fusion status into risk stratification and treatment allocation. Newer radiotherapy modalities hold promise for providing local control of disease while minimizing morbidity. The addition of traditional cytotoxic chemotherapeutic agents does not seem to improve outcomes in high-risk patients. Ultimately, the most substantial progress may arise from further elucidation of genetic and molecular pathways involved in RMS tumor formation in an effort to identify novel, targeted therapeutic approaches., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This article reviews common pediatric urologic cancers involving the genitourinary system. Rhabdomyosarcoma may occur in the bladder, prostate, paratesticular regions, vagina, or uterus. Some of these locations, such as the paratesticular region, have a more favorable outcome. Benign neoplasms account for the majority of pediatric testicular tumors and most are managed with testis-sparing surgery. Most genitourinary malignancies are expected to have a good outcome. One focus of treatment is organ preservation but not at the expense of a good oncologic outcome. Late sequelae of anticancer therapy are a concern and every attempt is made to decrease the intensity of tumor treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose of Review: To review on the most significant and recent developments in basic research, diagnostic, and therapeutic aspects of genitourinary rhabdomyosarcomas (RMS) in children., Recent Findings: Collaborative studies have dramatically improved therapy of genitourinary RMS with a remarkable improvement of survival. However, refractory or relapsed disease is still the most demanding challenge. Advances in our understanding of RMS molecular biology evolve new risk stratification and new therapeutic targets such as growth factors and their receptors. High-quality imaging is crucial and integrated fluorodeoxyglucose positron emission tomography/computed tomography significantly increased sensitivity. Alternative chemotherapeutical strategies were proven. Mutilating primary surgery should be avoided. Modern irradiation modalities with decrease of local radiation dose and, therefore, less long-term effects are new tools in the therapeutic arsenal of therapists., Summary: Therapy-associated morbidity after current RMS treatment can be significantly decreased by including modern strategies, especially in the field of irradiation. However, the follow-up is too short so far to make a distinct decision. The advances in understanding tumor biology may give rise to clinically relevant new therapeutic targets in the near future.

A 2-year-old intact female Golden Retriever presented due to rapidly progressing depression, ascites, dysuria, abdominal pain, and severe vaginal bleeding. At necropsy, the retroperitoneal space was expanded by multiple coalescing neoplastic nodules and the uterine wall was thickened with poorly defined neoplastic infiltrates. The urinary bladder was markedly thickened due to botryoid nodules exhibiting exophytic growth into the lumen. Metastases to lung, liver, kidney, and abdominal and thoracic lymph nodes were also noted. Microscopically, the genital tract and retroperitoneal masses were consistent with the alveolar subtype of rhabdomysarcoma, while the urinary bladder mass had characteristics of the embryonal subtype. Immunohistochemically, the neoplastic cells in all these tissue sites were intensely positive for desmin, sacromeric actin, and vimentin, while they were uniformly negative for cytokeratin and smooth muscle actin. Phosphotungstic acid hematoxylin stain revealed cross-striations in the cytoplasm of scattered neoplastic cells. Based on the gross findings, histopathology, and immunohistochemistry, genitourinary rhabdomyosarcoma with multisystemic metastases was made.

Objective: To study the clinicopathological, immunohistochemical and electron microscopic characteristics of pediatric rhabdomyosarcomas (RMS)., Methods: One hundred and forty-five cases of pediatric rhabdomyosarcomas were studied by routine histological, immunohistochemical and electron microscopic studies., Results: There were 97 male and 48 female patients with ages ranging from 4 months to 13 years and a mean of 4.2 years. The follow-up period of 100 patients was from 1 year to 20 years with a mean of 5 years after diagnosis. All cases were subtyped into the following histological categories: embryonal RMS, botryoid RMS, spindle cell RMS, alveolar RMS and solid RMS. Histopathological subtypes, tumor site and tumor stage correlated significantly with the patients' 5 years survival. The best prognosis was observed in spindle cell and botryoid RMS. Embryonal RMS carried an intermediate prognosis. Patients with alveolar RMS and solid RMS had the worst prognosis. Tumors involving bladder, head and neck carried a favorable clinical outcome. Patients with tumors involving trunk extremities retroperitoneum and pelvis did poorly. Immunohistochemically, all cases were positive for Vimentin. The positive staining rates for desmin, SMA and myoglobin were 78%, 75% and 37%, respectively. All tumors were negative for NSE, CD99 and LCA. Electron microscopy study showed features of myofilament and sarcomere in 10 of 15 cases., Conclusions: RMS is the most common soft tissue sarcoma of childhood. Immunohistochemistry and electron microscopy are helpful in diagnosis and classification of RMS.

Objective: Pseudosarcomatous myofibroblastic tumors (PMTs) of the urogenital tract are rare but distinctive lesions. Despite their benign behavior, they are frequently misinterpreted as leiomyosarcomas and rhabdomyosarcomas in preoperative biopsies and even in resected specimens because of their atypical spindle-cell features. Precise diagnosis of PMTs is important to avoid unnecessary radical therapy. We analyzed urogenital myoid tumors to clarify which of their characteristics are useful for the differential diagnosis., Methods: We evaluated 7 urogenital myoid tumors consisting of 3 PMTs, 2 leiomyosarcomas, and 2 rhabdomyosarcomas. We studied the expression of various immunohistochemical muscle-cell markers including desmin, muscle-specific actin, alpha-smooth muscle actin, high-molecular-weight caldesmon, and myogenin., Results: Desmin, muscle-specific actin, and alpha-smooth muscle actin were noted variably in all tumor types, whereas high-molecular-weight caldesmon was expressed only in leiomyosarcomas, and myogenin was expressed only in rhabdomyosarcomas., Conclusion: High-molecular-weight caldesmon and myogenin are useful for differentiating urogenital PMTs from myosarcomas.

Dramatic improvements have occurred in the treatment and prognosis of the child with rhabdomyosarcoma over the past 2 decades. Increased understanding of tumor behavior has improved survival and focused attention on important quality of life issues. Future therapeutic advances will depend largely on an improved molecular understanding of altered cell behavior and the continued efforts of multi-institutional studies.

Ectomesenchymomas (EM) are rare malignant neoplasms usually consisting of rhabdomyosarcoma (RMS) with a neural component. Only 21 cases have been previously reported. Here we extend the clinicopathologic spectrum of EM by describing our findings in 15 cases. Only 5 patients were infants; 10 were < or =3 years old and 5 were > or =6 years old. No male predilection was observed; 7 were female. The originating institutional diagnoses were; RMS (12), undifferentiated sarcoma (1), or EM (2), suggesting underdiagnosis of this entity. The primary tumor sites included external genital (5), pelvis/abdomen (6), head and neck (3), and extremity (1). The size of the primary neoplasm was usually > or =5 cm at diagnosis but dissemination only occurred in a minority. Local infiltration was not uncommon. These neoplasms were typically multilobate, thinly encapsulated, hemorrhagic, and necrotic. Light microscopic features were highly variable, but embryonal RMS with scattered or clustered ganglion cells, often in lacunae, was characteristic. In some cases, primitive neuroblastic or neuroectodermal areas were found and/or a component of alveolar RMS was seen. Focal anaplasia was occasionally observed. Mitotic activity appears higher than previously appreciated and some necrosis was invariably present. Electron microscopy was performed in 11 cases, which confirmed skeletal muscle +/- neural differentiation. Cytogenetic studies performed in five cases revealed no specific abnormality. Monoclonal neuron-specific enolase was the best marker of ganglion cells and primitive neural elements. MIC-2 (CD99) membrane expression was not definitively present in any of the six cases examined. A number of the above parameters appear to be of some prognostic significance, but overall, these neoplasms appear to have a similar outcome as would be predicted for their RMS element alone (exclusive of any neural component), with respect to the RMS subtype, age of the patient, and anatomic location of the neoplasm.

Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to arise from cells committed to a skeletal muscle lineage. With approximately 250 cases diagnosed yearly in the United States, it is the third most common extracranial solid tumor of childhood after Wilms' tumor and neuroblastoma. Important epidemiologic, biologic, and therapeutic differences have been elucidated within the RMS family. Common sites of primary disease include the head and neck region, genitourinary tract, and extremities. A site-based tumor-nodes-metastasis staging system is being incorporated into use for assessing prognosis and assigning therapy in conjunction with the traditional surgicopathologic clinical grouping system. The development of intensive multimodality treatment protocols tested in large-scale international trials has resulted in significant improvements in outcome, especially for patients with local or locally extensive disease for whom a 60%-70% disease-free survival can be expected. Despite aggressive approaches incorporating surgery, dose-intensive combination chemotherapy, and radiation therapy, the outcome for patients with metastatic disease remains poor. Future challenges include the development of less toxic therapy for patients with localized disease and new approaches for patients with metastatic disease.

Objective: The purpose of this study was to determine the incidence and CT imaging features of intraperitoneal rhabdomyosarcoma in children., Conclusion: Approximately 10% of children with rhabdomyosarcoma may have intraperitoneal neoplastic involvement either at the time of diagnosis or subsequently. On CT, intraperitoneal rhabdomyosarcomas are associated with ascites, enhancing nodules, masses, a pseudomyxoma peritonei-like appearance, and omental caking.

Rhabdomyosarcoma is the most common tumor of the lower genitourinary tract in children in the first 2 decades of life. Most cases of genitourinary rhabdomyosarcoma are of the embryonal histologic subtype and include tumors of the bladder, prostate, testes and paratesticular sites, penis, perineum, vagina, and uterus. The natural history, pattern of metastatic spread, treatment, and prognosis of childhood rhabdomyosarcoma vary with the anatomic site of the lesion. In children with rhabdomyosarcoma of the bladder or prostate, presenting signs and symptoms include urinary or fecal retention, dysuria, urinary tract infection, and hematuria. Paratesticular rhabdomyosarcoma produces painless scrotal swelling, which may be ignored until the tumor has reached a large size. Vaginal tumors may manifest as a prolapsing mass in the introitus. Radiologic studies of children with genitourinary rhabdomyosarcoma reflect the nonspecific gross features of the tumor, which may be ill defined with infiltrative margins or well circumscribed by a pseudocapsule of compressed tissue. The botryoid variant of embryonal rhabdomyosarcoma results when submucosal tumor produces a polypoid mass resembling a cluster of grapes within a hollow structure. Botryoid morphology is characteristic, but not specific, for rhabdomyosarcoma within the vagina or urinary bladder, since yolk sac tumor and "tumoral" cystitis may have a similar appearance. Invasion of adjacent structures by the primary tumor may make the precise anatomic origin of genitourinary rhabdomyosarcoma difficult to determine on cross-sectional images. Recent refinements in multidisciplinary therapeutic regimens combining chemotherapy, radiation therapy, and surgery have dramatically improved outcome for children with genitourinary rhabdomyosarcoma. Diagnostic imaging plays an important role in monitoring response to therapy.

Background: Survival for rhabdomyosarcoma appears to be more favorable in children and adolescents compared with adults. To determine the significance of age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data base., Methods: Pertinent prognostic variables, including age, TNM stage, histopathologic subtype, anatomic site, resectability, radiation to the primary site, and dose intensity of chemotherapy, were compared in a Cox proportional hazards model with mortality as the outcome variable., Results: Age at diagnosis (P = 0.0001) and local tumor invasiveness (P < 0.0001), distant parenchymal metastases (P < 0.0001), regional lymph node involvement (P = 0.0027), and histopathologic subtype (P = 0.0446) contributed information to the proportional hazards model., Conclusions: Age at diagnosis is an independent predictor of outcome in patients with rhabdomyosarcoma along with tumor invasiveness, metastases, regional lymph node involvement, and histopathologic subtype.

Current therapy for childhood sarcomas, particularly rhabdomyosarcomas, is a multidisciplinary effort requiring input from various specialists. Significant progress has been made in lower-stage disease because of advances in chemotherapy, radiotherapy, and surgery, but cure rates remain poor in high-stage lesions, and there is significant morbidity after treatment of lesions with a favorable outcome. Histologic classification is not always predictive of behavior, but recent modifications promise better prognostic significance. Great advances have also been made in our understanding of the biology of these lesions; these advances offer the promise of future therapeutic applicability. Detection of genetic alterations in predisposed individuals is possible but raises several significant nontherapeutic issues.

Magnetic resonance (MR) imaging, ultrasound, and computed tomography (CT) were performed for diagnosis and follow-up of rhabdomyosarcoma (RMS) arising from the genitourinary tract in five children, pelvic musculature in one, and the perineum in three others. MR imaging performed at 1.0 T included the following: spin-density-, T1-, and T2-weighted images in all nine patients; gadopentatate dimeglumine (Gd-DTPA)-enhanced T1-weighted images in five; and short TI inversion recovery (STIR) images in two children. Longitudinal T1-weighted images were of additional help in localizing the primary tumor at diagnosis and detecting local spread. Residual or recurrent disease within the bladder was best detected by spin-density images. Gd-DTPA enhancement improved contrast in two studies, but paramagnetic artifacts obscured intravesical lesions in three other studies. STIR images disclosed pelvic and retroperitoneal lymphadenopathy. MR imaging is recommended as the key method of diagnosis and follow-up of pelvic RMS.

The survival rates for childhood rhabdomyosarcomas have risen from 20% to 50% with the institution of a multidisciplinary approach involving the pediatric oncologist, radiation therapist, and surgeon. Increased survival has been particularly striking in the case of genitourinary rhabdomyosarcomas, which have a more favorable prognosis than rhabdomyosarcomas occurring in other anatomic sites. By stratifying genitourinary rhabdomyosarcomas by anatomic subgroup, i.e., paratesticular, bladder or bladder-prostate, and gynecologic, insight into specific predictors of failure can be obtained. Patients judged to be high risk at diagnosis can then be selected for more intensive or novel forms of therapy.

A total of 951 newly diagnosed patients with nonmetastatic rhabdomyosarcoma (RMS) under 21 years of age from four different cooperative study groups were analyzed to identify the most important pretreatment tumor characteristics in predicting survival. The patient characteristics considered were tumor invasiveness (T), tumor size, status of locoregional lymph nodes, and primary site. The cooperative groups and studies analyzed were: SIOP [RMS-75 (1975-1984)], the Intergroup Rhabdomyosarcoma Study [IRS-II (1978-1982)], Federal Republic of Germany [CWS-81 (1981-1986)] and Italy [RMS-79 (1979-1986), each study involving a different therapeutic protocol. Patient characteristics identified as having a significant relationship to survival by univariate analysis were (favorable features given in brackets): tumor invasiveness [T1], tumor size [less than or equal to 5 cm], status of locoregional lymph nodes [clinically negative], and primary site [orbit and genitourinary non-bladder prostate (GU-non-BP) sites]. T2 tumors tended to have large size (greater than 5 cm), to be associated with positive nodes, and to have a different distribution by primary site than T1 tumors. A multivariate Cox regression analysis of the pooled data identified tumor invasiveness (T), primary site, and the interaction between T and primary site as significant predictive factors for survival. The prognosis of orbital tumors was consistently favorable regardless of T status, whereas the prognosis for "other sites" was consistently unfavorable. International cooperation in this study has permitted the identification of good and poor risk patient subgroups, permitting the focusing of therapeutic protocols to particular risk groups and setting the stage for common future therapeutic protocols for rare subgroups of patients.

Seventeen children with rhabdomyosarcoma stage I to III diagnosed since 1973 are presented. The coordinated management utilizing surgical excision, irradiation (5000 rad) and systemic adjuvant multiagent chemotherapy is described. The favorable sites were head and neck sites and genitourinary region. The mean survival is at present 19 months. 14 children are alive and well. 13 children had no tumor recidivation, 1 child had 8 months after beginning of the therapy lung metastases which after irradiation with 2000 rad disappeared. 3 children (stage III) died 9, 14 and 20 months after diagnosis during therapy by metastases. Acute and late effects on normal tissues from radiation and chemotherapy were noted in 12 cases. A review of the literature and therapeutic alternatives in the future are indicated.

A series of 54 cases of embryonal rhabdomyosarcomas in adults were studied. The neoplasms were classified according to anatomic site, size, histologic pattern, age, and sex of the patients and modality of treatment. The major anatomic sites were the extremities (21 cases), genitourinary organs (13 cases) and the trunk (nine cases). The overall five-year survival rate was 21% but 79% of the patients were dead at an average time of 17 months after the primary diagnosis was made. On the other hand, 80% of the patients with Stage II disease (tumor size less than 5 cm) survived five years. In general, patients who were treated with surgery only or surgery and radiation or chemotherapy did much better than patients treated with chemotherapy and/or radiation therapy only. When the rate of recurrences, metastasis and time of death due to spread of neoplasm was compared in cases diagnosed between 1950-1969 and 1970-1978, patients in the last nine years had fewer recurrences, less metastases and better survival than those who had their neoplasm diagnosed and treated between 1950 and 1969.

A preliminary evaluation of histologic subtypes of rhabdomyosarcoma has shown that the alveolar pattern is associated with a significantly shorter survival when the patient has localized disease that has been completely excised at diagnosis. New histologic variants of undifferentiated sarcoma have been identified, but the clinical significance of these variants remains to be determined. Study of postmortem data of children placed on the Intergroup Rhabdomyosarcoma Study has shown several important clinical facts: Patients with head and neck parameningeal primary sites have a high incidence of treatment failures because the tumor extended into the adjacent central nervous system, with or without spinal fluid spread. Primary sites in the extremities and genitourinary tract are associated with an increased rate of regional lymph node spread. Systematic study of more patients is required before this association can be fully evaluated.

Histopathologic material from 1,782 patients registered in the Intergroup Rhabdomyosarcoma Study Committee (IRS)-I and -II were reviewed by the IRS Pathology Committee in order to provide a uniform approach to classification and correlate patient survival with tumor type. Categories considered eligible were the four types of rhabdomyosarcoma (RMS) (criteria of Horn and Enterline), extraosseous Ewing's tumor (EOE), and a group of somewhat variable undifferentiated sarcomas designated small round cell sarcoma, type indeterminate (STI). Tumors that were clearly sarcomas but were unclassifiable also were included (NOS). The committee diagnoses were embryonal (Emb) RMS in 877 (54%), alveolar (Alv) RMS in 343 (21%), botryoid (Botr) RMS in 88 (5%), pleomorphic (Pleo) RMS in 11 (1%), STI in 135 (8%), and EOE in 84 (5%). One in nine were mixtures of types, eg, Emb and Alv. Five percent of the sarcomas could not be classified because of inadequate material. In general, there was close agreement (94%) between the review committee and institutional pathologists in the diagnosis of RMS, but not in the specific types, particularly Alv RMS (41%) and STI (36%). This observation is important, since patients with Alv RMS and STI tumors had decreased survival compared with the other histologies. The prognosis varied by histology, with Botr having the best, Alv RMS and STI the worst, and Emb RMS and EOE an intermediate prognosis.

Clinico-pathologic reviews of series of children with rhabdomyosarcoma have yielded conflicting information regarding frequency of lymphatic spread of this disease. The 264 eligible entries in the Intergroup Rhabdomyosarcoma Study (from November 1972 to September 1975) have been categorized by a prospective staging system and pre-treatment characteristics and pathologic findings reviewed. Data accumulated thus far have revealed a higher than expected incidence of lymphatic metastases from extremity (17%) and genito-urinary sites (19%) with a somewhat lower incidence from the orbit (0%), the head and neck region (3%), and trunk (10%). These differences in regard to lymphatic metastases were found to have no relationship to age, sex, tumor size, or histologic type when these factors were simultaneously examined.

A histopathological and immunoperoxidase study on three cases of genitourinary gangliorhabdomyosarcoma using a spectrum of conventional staining methods and antibodies against myoglobin, neuron-specific enolase and S-100 protein is presented. The results of the study have shown that differentiated myoblasts, ganglion cells and Schwann cells reacted positively with the particular antisera, but the majority of undifferentiated cells were negative. From the immunopathology results it was not possible to determine whether the undifferentiated cells were precursors of neural cells or myoblasts; the histological appearance resembled that of mesenchymal cells commonly seen in rhabdomyosarcomas. Theories concerning the origin of these tumours from neural crest ectomesenchyme or from neural crest and somitic mesenchyme are considered. Further study is needed to establish their histogenesis.

The characteristics of 554 evaluated patients entered into a clinical trial conducted by the Pediatric Intergroup Rhabdomyosarcoma Committee between November 1972 and September 1978 were examined for their relationship to prognosis. Prognosis was defined as disease-free time and overall survival time in clinical groups I and II and time on study and survival time in clinical groups III and IV; all times were measured from the start of treatment. The percentage of patients surviving 2 years differed significantly among the clinical groups: I, 92; II, 78; III, 64; and IV, 35. The percentage of patients free of disease at 2 years was significantly higher in group I than in group II (83 vs. 72%, respectively); P = 0.02. The patient characteristics of group I most related to disease-free and overall survival were histologic cell type (alveolar, unfavorable), lymphocyte count (low count, unfavorable), and primary site (disease in extremities, unfavorable). In group II, sex (male, favorable) and lymphocyte count (low count, unfavorable) were significantly related to disease-free and overall survival times. Patients in the clinical subgroup with both microscopic residual disease and lymph node metastasis had poorer survival than patients in other subgroups. Primary site of disease was the only characteristic of group III related to length of time on study and to survival. Orbit and the genitourinary system were favorable primary sites, whereas the retroperitoneal area and extremities were unfavorable. In group IV, primary site (genitourinary, favorable) was related to length of time on study and survival. Sex (male, favorable) was related to survival experience.

The patient was a 2-year-old boy, who was brought to our clinic with the chief symptom of urinary retention. We suspected retrovesical tumor by digital examination, intravenous pyelography and retrograde cystography. Surgery was performed and the bladder and prostate including the tumor were removed. Ureterocutaneostomy was constructed on both sides. The pathohistological diagnosis was rhabdomyosarcoma (embryonal type). Thereafter, chemotherapy and irradiation were applied, but the patient died of cachexia which was clinically caused by a local recurrence, fourteen months after the operation. Forty-six cases of retrovesical sarcoma were collected from the recent Japanese literature, and reviewed.

Between 1972 and 1978, 780 patients were entered on the Intergroup Rhabdomyosarcoma Study. The results indicated that postoperative irradiation of the tumor bed was unnecessary when vincristine, dactinomycin, and cyclophosphamide (VAC) were given in combination for 2 years after excision of a localized tumor (group I). This drug combination was no better than vincristine combined with dactinomycin given to patients with grossly resected tumors (group II) who also received postoperative irradiation. Intensive chemotherapy regimens, "pulse" VAC alone or VAC combined with adriamycin followed by irradiation, were equally effective in advanced stages and induced tumor regression in 85% of the patients who had gross residual disease after surgery (group III) and in 68--74% of the patients with metastatic disease at diagnosis (group IV). Two-year relapse-free survival rates were projected to be 83% for group I, 72% for group II, 65% for group III, and 28% for group IV; the overall survival rates were higher for each group. Patients with local and distant recurrences had equally poor prognoses.

Rhabdomyosarcoma of the spermatic cord is a rare, highly malignant lesion, for which the optimum treatment has yet to be ascertained. Results of treatment of 3 patients are presented, making the total reported experiences 53 cases. Two of our 3 patients are alive. One survivor underwent retroperitoneal lymphadenectomy and the other received radical orchiectomy only. The third patient had metastasis at the time of diagnosis and subsequently died. Because of a paucity of knowledge concerning the disease, its propensity for youthful patients and its highly malignant characteristics, all treatment modalities must be considered and tailored to the needs of the individual patient.